Bacteriophage compositions and uses thereof

Abstract

The present invention includes compositions and methods for increasing antibiotic sensitivity and/or decreasing virulence in bacteria.

What is claimed is: 
     
         1 . A method of increasing antibiotic sensitivity and/or decreasing virulence in a pathogenic bacteria, the method comprising:
 contacting the bacteria with a lytic bacteriophage selected from the group consisting of OMKO1, LPS-5, TIVP-H6, LPS-TLTL,TIVP-27, SFA1-1, SF60B, SFNHSI, SF37B, PG-I1, and U136B.   
     
     
         2 . The method of  claim 1 , wherein the bacteria are contacted with bacteriophage at a multiplicity of infection of bacteriophage to bacteria in the range of about 0.05 to about 50. 
     
     
         3 . The method of  claim 1 , wherein the bacteriophage binds at least one molecule selected from the group consisting of an O-antigen, efflux pump, Type IV pilus, LPS (core), OmpA, OmpC, TolC, and peptidoglycan in the bacteria. 
     
     
         4 . The method of  claim 1 , wherein the bacteriophage binds TolC and LPS. 
     
     
         5 . The method of  claim 1 , wherein the bacteriophage binds a protein of a Mex efflux pump. 
     
     
         6 . The method of  claim 5 , wherein the Mex efflux pump is a surface exposed protein. 
     
     
         7 . The method of  claim 5 , wherein the Mex protein is selected from the group consisting of OprM, MexA, MexB, MexX, and MexY. 
     
     
         8 . The method of  claim 1  further comprising contacting the pathogenic bacteria with an antibiotic. 
     
     
         9 . The method of  claim 1 , wherein the pathogenic bacteria is drug resistant. 
     
     
         10 . The method of  claim 1 , wherein the pathogenic bacteria is a multi-drug resistant (MDR) bacteria. 
     
     
         11 . The method of  claim 1 , wherein the bacteriophage comprises a nucleotide sequence at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOs: 1-13. 
     
     
         12 . The method of  claim 1 , wherein the bacteriophage is administered to a subject in need thereof. 
     
     
         13 . A pharmaceutical composition comprising one or more lytic bacteriophages selected from the group consisting of OMKO1, LPS-5, TIVP-H6, LPS-TLTL, TIVP-27, SFA1-1, SF60B, SFNHSI, SF37B, PG-I1, and U136B. 
     
     
         14 . The pharmaceutical composition of  claim 13 , wherein the bacteriophage binds at least one molecule selected from the group consisting of an O-antigen, Type IV pilus, LPS (core), OmpA, OmpC, TolC, and peptidoglycan on multi-drug resistant (MDR) bacteria. 
     
     
         15 . The pharmaceutical composition of  claim 13 , wherein the one or more bacteriophages comprise a nucleotide sequence at least 80%, 85%, 90%, 95%, 96%, 97% 98%, 99%, or 100% identical to any one of SEQ ID NOs: 1-13. 
     
     
         16 . The pharmaceutical composition of  claim 13 , further comprising an antibiotic. 
     
     
         17 . A method of treating a bacterial infection in a subject in need thereof, the method comprising administering the pharmaceutical composition of  claim 13  to the subject with the bacterial infection. 
     
     
         18 . The method of  claim 17 , wherein the pharmaceutical composition is administered directly to a site of the bacterial infection. 
     
     
         19 . The method of  claim 17 , further comprising administering an antibiotic to the subject. 
     
     
         20 . The method of  claim 19 , wherein the antibiotic is administered before or after or co-administered with the pharmaceutical composition. 
     
     
         21 . The method of  claim 17 , wherein the bacterial infection is drug resistant. 
     
     
         22 . The method of  claim 17 , wherein the bacterial infection is multi-drug resistant. 
     
     
         23 . The method of  claim 1 , wherein the pathogenic bacteria is associated with a biofilm. 
     
     
         24 . The method of  claim 1 , wherein the pathogenic bacteria is  Pseudomonas aeruginosa , a  Shigella  species,  Staphylococcus aureus , or  Escherichia coli.    
     
     
         25 . The method of  claim 24 , wherein the pathogenic bacteria is in a biofilm. 
     
     
         26 . A method of disrupting a pathogenic bacteria associated with a biofilm, the method comprising contacting the bacteria with a lytic bacteriophage selected from the group consisting of OMKO1, LPS-5, TIVP-H6, LPS-TLTL, TIVP-27, SFA1-1, SF60B, SFNHSI, SF37B, PG-I1, and U136B. 
     
     
         27 . A method of preventing formation of a biofilm on a surface, the method comprising contacting the surface with a lytic bacteriophage selected from the group consisting of OMKO1, LPS-5, TIVP-H6, LPS-TLTL, TIVP-27, SFA1-1, SF60B, SFNHSI, SF37B, PG-I1, and U136B. 
     
     
         28 . The method of  claim 26 , wherein the bacteriophage binds a molecule selected from the group consisting of an O-antigen, efflux pump, Type IV pilus, LPS (core), OmpA, OmpC, and TolC in the bacteria and the bacteria either genetically resists bacteriophage infection or becomes infected and lysed by the bacteriophage, and wherein genetically resistant bacteria have impaired efflux pumps and increased sensitivity to one or more antibiotics. 
     
     
         29 . The method of  claim 26 , further comprising contacting the bacteria or surface with the one or more antibiotics. 
     
     
         30 . A composition comprising an LPS-5 bacteriophage targeting  Pseudomonas aeruginosa , the bacteriophage having a genome comprising a nucleic acid sequence comprising SEQ ID NO: 1. 
     
     
         31 . A composition comprising an OMKO1 bacteriophage targeting  Pseudomonas aeruginosa , the bacteriophage having a genome comprising a nucleic acid sequence comprising SEQ ID NO: 2. 
     
     
         32 . A composition comprising a TIVP-H6 bacteriophage targeting  Pseudomonas aeruginosa , the bacteriophage having a genome comprising a nucleic acid sequence comprising SEQ ID NO: 3. 
     
     
         33 . A composition comprising an LPS-TLTL bacteriophage targeting  Pseudomonas aeruginosa , the bacteriophage having a genome comprising a nucleic acid sequence comprising SEQ ID NO: 4. 
     
     
         34 . A composition comprising an TIVP-27 bacteriophage targeting  Pseudomonas aeruginosa , the bacteriophage having a genome comprising a nucleic acid sequence comprising SEQ ID NO: 5. 
     
     
         35 . A composition comprising an SFA1-1 bacteriophage targeting a  Shigella  spp. bacteria, the bacteriophage having a genome comprising a nucleic acid sequence comprising SEQ ID NO: 6. 
     
     
         36 . A composition comprising an SF60B bacteriophage targeting a  Shigella  spp. bacteria, the bacteriophage having a genome comprising a nucleic acid sequence comprising SEQ ID NO: 7. 
     
     
         37 . A composition comprising an SFNHSI bacteriophage targeting a  Shigella  spp. bacteria, the bacteriophage having a genome comprising a nucleic acid sequence comprising SEQ ID NO: 8. 
     
     
         38 . A composition comprising an SF37B bacteriophage targeting a  Shigella  spp. bacteria, the bacteriophage having a genome comprising a nucleic acid sequence comprising SEQ ID NO: 9. 
     
     
         39 . A composition comprising a PG-I1 bacteriophage targeting  Staphylococcus aureus , the bacteriophage having a genome comprising at least one nucleic acid sequence selected from the group consisting of SEQ ID NOs: 10-12. 
     
     
         40 . A composition comprising a U136B bacteriophage targeting  E. coli , the bacteriophage having a genome comprising a nucleic acid sequence comprising SEQ ID NO: 13. 
     
     
         41 . A method of treating a bacterial infection in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a composition according to  claim 23 . 
     
     
         42 . The method of  claim 41 , wherein the bacterial infection is drug-resistant or multi-drug resistant.